Abstract 2009: Co-expression of interleukin-4 receptor alpha and KRAS correlates with disease severity and prognosis in pancreatic cancer patients

Abstract Introduction: There will be 66, 400 new cases of pancreatic cancer identified and 51, 750 will die by end of 2024 in the United States. KRAS is the most common oncogenic driver occurring in ≥85% of pancreatic cancer patients. Previously, we identified an overexpression of high affinity binding protein Interleukin-4 Receptor alpha (α) of Interleukin 4 (IL-4) in numerous solid human cancers including pancreatic cancer. Herein, we investigated if IL-4Rα and KRAS co-expression can act as a biomarker of disease severity in pancreatic cancer patients. Experimental: One hundred and seven archival tumor specimens were examined by six investigators for IL-4Rα and KRAS expression by IHC and ISH techniques in a blinded manner. The data were stratified into pathological grades and stages of the patients. The results were analyzed statistically if individual/combined expression of IL-4Rα or KRAS can serve as biomarker/s of disease severity. Kaplan-Meier survival analysis was performed to investigate if these gene-expression had any influence on overall survival of the patients. Results: Our IHC results demonstrate that ≥68% samples overexpressed IL-4Rα alone in moderately to poorly differentiated grade tumors and in samples from clinical stage II + III patients with ≥2+ immunostaining intensity. Interestingly, ≥80 % of the specimens with moderately to poorly differentiated grades showed a co-expression for KRAS and IL-4Rα (≥2+). In contrast, patients with well differentiated grade and clinical stage I revealed ≤ 73% co-expression of these genes. We observed a similar pattern of mRNA expression in these patients by ISH. Further, Kaplan-Meier analysis revealed a significantly shorter survival (P≤0.001) in patients with ≥2+ positive expression of IL-4Rα plus KRAS in moderately to poorly differentiated grades and advanced clinical stages. In contrast, the patients overexpressing either of these genes alone, regardless of grades and stages, survived relatively longer compared to those expressing both IL-4Rα and KRAS . Summary and Conclusion: Our data show that IL-4Rα and KRAS co-expression, correlate with disease severity in pancreatic cancer patients. Thus our study uncovers a novel role of combined expression of IL-4Rα and KRAS as a biomarker of prognosis and driver of oncogenesis in pancreatic cancer patients and may serve a unique druggable target/s for developing targeted cellular or gene therapy-based cancer immunotherapies. Citation Format: Ashley Lea, Toshio Fujisawa, Hiroyuki Isayama, Supreet Khanal, Santosh Panthi, Mona Mansouri, Samir Lababidi, Steven R. Bauer, Kyung Sung, Nirjal Bhattarai, Bharat H. Joshi. Co-expression of interleukin-4 receptor alpha and KRAS correlates with disease severity and prognosis in pancreatic cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2009.